Dosing & Uses
Dosage Forms & Strengths
ertugliflozin/sitagliptin
tablet
- 5mg/100mg
- 15mg/100mg
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both ertugliflozin and sitagliptin is appropriate
5 mg/100 mg PO qDay in morning initially; if additional glycemic control is needed and starting dose is tolerated, may increase to maximum dose of 15 mg/100 mg
Patients on ertugliflozin: Maintain ertugliflozin dose when switched to combination
Dosage Modifications
Concomitant use with insulin and insulin secretagogues may increase the risk of hypoglycemia; lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with ertugliflozin
Renal impairment
- eGFR ≥45 mL/min/1.73 m²: No dosage adjustment necessary
- eGFR <45 mL/min/1.73 m²: Not recommended
- Severe (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or dialysis: Contraindicated
Hepatic impairment
- Mild-to-moderate: No dosage adjustment necessary
- Severe: Not recommended
Dosing Considerations
Assess renal function before initiating and as clinically indicated
In patients with volume depletion, correct this condition before initiating
Limitations of use
- Not recommended in patients with type 1 diabetes mellitus; may increase risk of diabetic ketoacidosis in these patients
- Not studied in patients with history of pancreatitis; unknown if drug increases risk for pancreatitis
<18 years: Safety and efficacy not established
≥65 years: No dosage adjustment necessary
Patients aged ≥65 years had a higher incidence of adverse reactions related to volume depletion compared with younger patients
Elderly patients are more likely to have decreased renal function; because renal function abnormalities can occur after initiating ertugliflozin, and sitagliptin is known to be substantially excreted by the kidneys, renal function should be assessed more frequently
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (5)
- erdafitinib
erdafitinib will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- ethanol
ethanol, sitagliptin. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.
- lasmiditan
lasmiditan increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- sotorasib
sotorasib will decrease the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- tepotinib
tepotinib will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
Monitor Closely (84)
- albiglutide
albiglutide, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- aripiprazole
aripiprazole, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- asenapine
asenapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- atazanavir
atazanavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- benazepril
sitagliptin increases toxicity of benazepril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of adverse/toxic effects, specifically, increased risk of angioedema.
- berotralstat
berotralstat will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- bexarotene
bexarotene increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.
- bitter melon
bitter melon increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
- bosutinib
bosutinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- captopril
sitagliptin, captopril. Either increases effects of the other by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of adverse/toxic effects, specifically increased risk of angioedema.
- chlorpropamide
ertugliflozin, chlorpropamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- cinnamon
cinnamon increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
- ciprofloxacin
ciprofloxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.
- clozapine
clozapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- crizotinib
crizotinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- darunavir
darunavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- dulaglutide
dulaglutide, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- elagolix
elagolix will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- eliglustat
eliglustat increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- exenatide injectable solution
exenatide injectable solution, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- exenatide injectable suspension
exenatide injectable suspension, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- fleroxacin
fleroxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- fosamprenavir
fosamprenavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- fostamatinib
fostamatinib will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- gemifloxacin
gemifloxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- glimepiride
ertugliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- glipizide
ertugliflozin, glipizide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- glyburide
ertugliflozin, glyburide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- ifosfamide
ifosfamide, ertugliflozin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Monitor renal function in patients with severe renal impairment, severe intestinal inflammation, or prolonged use >2 gm/day.
- iloperidone
iloperidone, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- indinavir
indinavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- insulin aspart
ertugliflozin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin aspart protamine/insulin aspart
ertugliflozin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin degludec
sitagliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
ertugliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin. - insulin degludec/insulin aspart
sitagliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- insulin detemir
ertugliflozin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin detemir
sitagliptin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- insulin glargine
ertugliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin glulisine
ertugliflozin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin inhaled
ertugliflozin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin isophane human/insulin regular human
ertugliflozin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin lispro
ertugliflozin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
sitagliptin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin lispro protamine/insulin lispro
sitagliptin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
ertugliflozin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin. - insulin NPH
sitagliptin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
ertugliflozin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin. - insulin regular human
sitagliptin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
ertugliflozin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin. - istradefylline
istradefylline will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
- lonapegsomatropin
lonapegsomatropin decreases effects of ertugliflozin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
- ivacaftor
ivacaftor increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ketotifen, ophthalmic
ketotifen, ophthalmic, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
- levofloxacin
levofloxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- liraglutide
liraglutide, sitagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- lomitapide
lomitapide increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
- lonafarnib
lonafarnib will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- lonapegsomatropin
lonapegsomatropin decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
- lopinavir
lopinavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- lurasidone
lurasidone, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- marijuana
marijuana decreases effects of sitagliptin by pharmacodynamic antagonism. Use Caution/Monitor.
- mecasermin
mecasermin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
- mifepristone
mifepristone will increase the level or effect of sitagliptin by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor
- moxifloxacin
moxifloxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- nateglinide
ertugliflozin, nateglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- nelfinavir
nelfinavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- ofloxacin
ofloxacin increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- olanzapine
olanzapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- opuntia ficus indica
opuntia ficus indica increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor.
- paliperidone
paliperidone, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- ponatinib
ponatinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- quetiapine
quetiapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- repaglinide
ertugliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- risperidone
risperidone, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- ritonavir
ritonavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- saquinavir
saquinavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- sarecycline
sarecycline will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- shark cartilage
shark cartilage increases effects of sitagliptin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
- somapacitan
somapacitan decreases effects of ertugliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .
somapacitan decreases effects of sitagliptin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. . - stiripentol
stiripentol will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.
- tolazamide
ertugliflozin, tolazamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- sulfamethoxypyridazine
sulfamethoxypyridazine increases effects of sitagliptin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
- tenofovir DF
tenofovir DF, sitagliptin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- teriflunomide
teriflunomide increases levels of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.
- tipranavir
tipranavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- tolbutamide
ertugliflozin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension decreases effects of sitagliptin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.
Minor (75)
- agrimony
agrimony increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- American ginseng
American ginseng increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- amitriptyline
amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- amoxapine
amoxapine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- anamu
anamu increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
- bendroflumethiazide
bendroflumethiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- budesonide
budesonide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- chlorothiazide
chlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chlorpropamide
sitagliptin, chlorpropamide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- chlorthalidone
chlorthalidone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chromium
chromium increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- clomipramine
clomipramine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- clonidine
clonidine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
clonidine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production. - cornsilk
cornsilk increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- cortisone
cortisone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- cyclopenthiazide
cyclopenthiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- damiana
damiana decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
- danazol
danazol increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- desipramine
desipramine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- devil's claw
devil's claw increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- dexamethasone
dexamethasone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- digoxin
sitagliptin increases levels of digoxin by unspecified interaction mechanism. Minor/Significance Unknown.
- doxepin
doxepin increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- elderberry
elderberry increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
- eucalyptus
eucalyptus increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
- fludrocortisone
fludrocortisone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- fluoxymesterone
fluoxymesterone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- fo-ti
fo-ti increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- forskolin
forskolin increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
- glimepiride
sitagliptin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- glipizide
sitagliptin, glipizide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- glyburide
sitagliptin, glyburide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- gotu kola
gotu kola increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
- guanfacine
guanfacine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
guanfacine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production. - gymnema
gymnema increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- horse chestnut seed
horse chestnut seed increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- hydrochlorothiazide
hydrochlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- hydrocortisone
hydrocortisone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- imipramine
imipramine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- indapamide
indapamide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- isoniazid
isoniazid decreases effects of sitagliptin by unspecified interaction mechanism. Minor/Significance Unknown.
- juniper
juniper increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- lofepramine
lofepramine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- lycopus
lycopus increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- maitake
maitake increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).
- maprotiline
maprotiline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- mesterolone
mesterolone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- methyclothiazide
methyclothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- methylprednisolone
methylprednisolone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- methyltestosterone
methyltestosterone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- metolazone
metolazone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- nettle
nettle increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
- nortriptyline
nortriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- ofloxacin
ofloxacin, sitagliptin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
- oxandrolone
oxandrolone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- oxymetholone
oxymetholone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- pegvisomant
pegvisomant increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- potassium acid phosphate
potassium acid phosphate increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- potassium chloride
potassium chloride increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- potassium citrate
potassium citrate increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- prednisolone
prednisolone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- prednisone
prednisone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- protriptyline
protriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- sage
sage increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- stevia
stevia increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- testosterone
testosterone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- testosterone buccal system
testosterone buccal system increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- testosterone topical
testosterone topical increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- tolazamide
sitagliptin, tolazamide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- tolbutamide
sitagliptin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.
- tongkat ali
tongkat ali increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
- trazodone
trazodone increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- trimipramine
trimipramine increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- vanadium
vanadium increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
Adverse Effects
>10% (Ertugliflozin)
Female genital mycotic infections (9.1-12.2%)
1-10% (Ertugliflozin)
Volume depletion adverse effects (1.9-4.4%)
Male genital mycotic infections (3.7-4.2%)
Urinary tract infections (4-4.1%)
Headache (2.9-3.5%)
Vaginal pruritus (2.4-2.8%)
Increased urination (2.4-2.7%)
Nasopharyngitis (2-2.5%)
Back pain (1.7-2.5%)
Renal adverse effects (1.3-2.5%)
Weight decreased (1.2-2.4%)
Thirst (1.4-2.7%)
Frequency Not Defined (Sitagliptin)
Upper respiratory tract infection
Nasopharyngitis
Headache
Abdominal pain
Nausea
Diarrhea
Peripheral edema
Postmarketing Reports (Sitagliptin)
Hypersensitivity including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions
Hepatic enzyme elevations
Acute pancreatitis
Worsening renal function and acute renal failure
Bullous pemphigoid
Constipation
Vomiting
Headache
Myalgia
Pain in extremity
Back pain
Pruritus
Rhabdomyolysis
Tubulointerstitial nephritis
Warnings
Contraindications
Hypersensitivity to drugs or excipients; reactions such as angioedema or anaphylaxis have occurred
Severe renal impairment (<30 mL/min/1.73 m2), end-stage renal disease, or dialysis
Cautions
Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin reported; promptly discontinue if pancreatitis suspected
Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, with low systolic blood pressure, on diuretics, or who are elderly; before initiating treatment in patients with one or more of risk factors, assess volume status and renal function
Renal impairment may occur owing to intravascular volume contraction; before initiating, consider factors that may predispose patients to acute kidney injury, including hypovolemia, chronic renal insufficiency, CHF, and concomitant medications (eg, diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing ertugliflozin in any setting of reduced oral intake or fluid loss; monitor for signs and symptoms of acute kidney injury, and, if evident, discontinue drug promptly and institute treatment
Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization reported in patients receiving SGLT2 inhibitors
Heart failure has been observed in cardiovascular outcomes trials for 2 other DPP-4 inhibitors; consider the risks and benefits prior to initiating treatment in patients at risk for heart failure (eg, those with a prior history of heart failure, a history of renal impairment), and observe these patients for signs and symptoms of heart failure during therapy
Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible
Serious hypersensitivity reported with sitagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions, including Stevens-Johnson syndrome (see Contraindications)
Dose-related increases in LDL-C reported
Severe and disabling arthralgia reported in patients taking DDP-4 inhibitors; may occur at any time; symptoms relieved upon discontinuation
Bullous pemphigoid requiring hospitalization reported with DPP-4 inhibitors; patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor
No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
Lower limb amputation
- An increased risk for lower limb amputation (primarily of the toe) has been observed in clinical studies with another SGLT2 inhibitor; before initiating, consider factors that may predispose patient to increased risk of amputations (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)
- Counsel patients about importance of routine preventative foot care; monitor patients receiving drug for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue therapy if these complications occur
Ketoacidosis
- Not indicated for patients with type 1 diabetes mellitus (T1DM); in placebo-controlled trials, risk of ketoacidosis was increased in patients with T1DM who received SGLT2 inhibitors
- Risk of ketoacidosis may be greater with higher doses
- Before initiating therapy, consider factors in patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
- Consider temporarily discontinuing therapy for at least 4 days for patients who undergo scheduled surgery
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restarting therapy
- Educate patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur
Drug interaction overview
- Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
- Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
- Monitoring glycemic control with 1,5-AG assay is not recommended, as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
- Coadministration with sitagliptin has shown a slight increase in digoxin AUC (11%) and mean peak drug concentration (18%); no dosage adjustment of digoxin require, but monitor appropriately
Pregnancy
Pregnancy
Ertugliflozin
- Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
- Data are limited in pregnant women and are not sufficient to determine a drug-associated risk of adverse developmental outcomes; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
Animal data
- In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy; doses ~13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible
- There was no evidence of fetal harm in rats or rabbits at exposures of ertugliflozin ~300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis
Sitagliptin
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to sitagliptin during pregnancy
- Health care providers are encouraged to report any prenatal exposure by calling the Pregnancy Registry at 1-800-986-8999
Lactation
Not recommended while breastfeeding
Unknown if distributed in human breast milk
Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney
Because of the potential for serious adverse reactions in a breastfed infant, advise women that ertugliflozin/sitagliptin is not recommended while breastfeeding
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Ertugliflozin: Selective sodium-glucose transporter-2 (SGLT2) inhibitor; lowers the renal glucose threshold (ie, the plasma glucose concentration which exceed the maximum glucose reabsorption capacity of the kidney); lowering the renal glucose threshold results in increased urinary glucose excretion
Sitagliptin: Dipeptyl peptidase-IV (DPP-4) inhibitor; increases and prolongs incretin hormone activity, which is inactivated by DPP-4 enzyme; incretins increase insulin release and synthesis from pancreatic beta cells and reduce glucagon secretion from pancreatic alpha cells
Absorption
Ertugliflozin
- Peak plasma time: 1 hr (fasting); 2 hr (high-fat, high-caloric meal)
- Peak plasma concentration, steady-state: 81.3 ng/mL (5 mg qDay); 268 ng/mL (15 mg qDay)
- AUC, steady-state: 398 ng⋅hr/mL (5 mg qDay); 1,193 ng⋅hr/mL (15 mg qDay)
- Steady-state is reached after 4-6 days
- Bioavailability, 15 mg dose: ~100%
Sitagliptin
- Peak plasma time: 1 hr
- Bioavailability: 87%
Distribution
Ertugliflozin
- Vd, steady-state: 85.5 L
- Protein binding: 93.6%
- Blood-to-plasma concentration ratio of ertugliflozin: 0.66
Sitagliptin
- Vd: 198 L
- Protein binding: 38%
Metabolism
Ertugliflozin
- Major metabolic pathway for ertugliflozin is UGT1A9 and UGT2B7-mediated O-glucuronidation to 2 glucuronides (pharmacologically inactive at clinically relevant concentrations)
- CYP-mediated (oxidative) metabolism of ertugliflozin is minimal (12%)
Sitagliptin
- Primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8
Ertugliflozin
- Half-life: 16.6 hr
- Clearance: 11.2 L/hr
- Excretion, oral [14C]-ertugliflozin solution: Feces (40.9%); urine (50.2%)
- Excretion, unchanged ertugliflozin: Feces (33.8%); urine (1.5%)
Sitagliptin
- Half-life: 12.4 hr
- Renal clearance: 350 mL/min
- Excretion: 87% urine; 13% feces
Administration
Oral administration
Take in the morning qDay, with or without food
Missed dose
- Take it as soon as you remember
- If it is almost time for scheduled next dose, skip missed dose and take the next regularly scheduled time
- Do not take 2 doses of ertugliflozin at the same time
Storage
Store at room temperature between 68-77°F (20-25°C)
Keep tablets dry
Store blister packs in the original package
Images
Formulary
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